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1.广西中医药大学 研究生院,南宁 530001
2.广西中医药大学 第一附属医院,南宁 530001
王金鑫,在读硕士,从事脾胃四时调五脏防治疾病的应用研究,E-mail:1185884631@qq.com
谭金晶,主治医师,博士,从事脾胃四时调五脏防治疾病的应用研究,E-mail:1730397922@qq.com
收稿日期:2022-08-10,
网络出版日期:2022-09-15,
纸质出版日期:2022-12-20
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王金鑫,谢胜,黎丽群等.基于JAK/STAT通路的中医药干预溃疡性结肠炎研究进展[J].中国实验方剂学杂志,2022,28(24):274-282.
WANG Jinxin,XIE Sheng,LI Liqun,et al.Traditional Chinese Medicine Intervention in Ulcerative Colitis Based on JAK/STAT Pathway: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(24):274-282.
王金鑫,谢胜,黎丽群等.基于JAK/STAT通路的中医药干预溃疡性结肠炎研究进展[J].中国实验方剂学杂志,2022,28(24):274-282. DOI: 10.13422/j.cnki.syfjx.20221516.
WANG Jinxin,XIE Sheng,LI Liqun,et al.Traditional Chinese Medicine Intervention in Ulcerative Colitis Based on JAK/STAT Pathway: A Review[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(24):274-282. DOI: 10.13422/j.cnki.syfjx.20221516.
溃疡性结肠炎(UC)是以结直肠黏膜慢性持续性炎症为表现的疾患,该病病理机制复杂,与免疫炎症及凋亡活性增强等有关。Janus酪氨酸蛋白激酶(JAK)/信号转导及转录激活因子(STAT)是调控机体生理功能的重要分子通路,可调控肠道促炎因子的释放和诱导细胞凋亡,造成结肠组织损伤。UC状态下,JAK与STAT的生物活性及表达水平均上升,组织炎症反应及凋亡率增加,促使肠黏膜组织遭受破坏。目前,UC的治疗主要使用糖皮质激素、免疫抑制剂等减轻肠道炎症,虽然可以在一定程度上阻遏UC的进展,但不良反应较大。大量研究表明,中医药防治UC具有明显的优势,可显著降低该病复发率。近年来,中医药界开展了大量研究探索中医药通过调控JAK/STAT通路治疗UC的作用,结果表明JAK/STAT通路是中医药治疗UC的关键靶通路。基于虚实夹杂的病因病机,中医药以清热燥湿、凉血活血、健脾温肾和攻补兼施等法调控JAK/STAT通路,维持促炎因子与抗炎因子平衡,削弱结肠炎症反应,抑制细胞凋亡,起到治疗UC的作用。该文总结和分析了中医药靶向JAK/STAT信号通路干预UC的机制和作用,并将不同细胞因子如白细胞介素(IL)-6、IL-10、IL-23、microRNA(miRNA)-146a、细胞因子信号转导抑制因子2/3(SOCS2/3)等作用于多种JAK/STAT信号通路家族亚型的分子机制整合起来,使科研人员更为全面认识中医药对UC中JAK/STAT通路的作用机制提供帮助,以期为UC的治疗及进一步的药物开发提供理论依据。
Ulcerative colitis(UC)is a disease characterized by chronic persistent inflammation of the colorectal mucosa. Its complex pathological mechanism is related to immune inflammation and enhanced apoptotic activity. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT)is an important regulatory pathway in the body's physiological function
which can regulate the release of intestinal pro-inflammatory factors and induce apoptosis
resulting in colon tissue damage. In the condition of UC
the biological activities and expression levels of JAK and STAT increased
and the tissue inflammatory response and apoptosis rate increased
which led to the destruction of intestinal mucosal tissues. At present
in the treatment of UC
glucocorticoids and immunosuppressants are mainly employed to reduce intestinal inflammation. Although they can block the progress of UC to some extent
the adverse reactions are severe. A large number of studies have shown that traditional Chinese medicine(TCM) has significant advantages in the prevention and treatment of UC and can significantly reduce the recurrence rate of this disease. In recent years
plenty of studies have been carried out to explore the role of TCM in the treatment of UC by regulating the JAK/STAT pathway. The results have shown that the JAK/STAT pathway is the key target pathway of TCM in the treatment of UC. Based on the etiology and pathogenesis of deficiency and excess
TCM regulates the JAK/STAT pathway by clearing heat
drying dampness
cooling and activating blood
invigorating the spleen
warming the kidney
and performing both tonification and elimination to maintain the balance between pro-inflammatory factors and anti-inflammatory factors
weaken colonic inflammatory response
inhibit apoptosis
and play a role in the treatment of UC. The present study analyzed the mechanism and effect of TCM in intervening in UC by targeting the JAK/STAT signaling pathway and summarized the molecular mechanisms of different cytokines such as interleukin-6(IL-6)
IL-10
IL-23
microRNA(miRNA)-146a
and suppressors of cytokine signaling 2/3(SOCS2/3) on many family subtypes of the JAK/STAT signaling pathway to facilitate the comprehensive understanding of researchers on the mechanism of TCM on the JAK/STAT pathway in UC
which is expected to provide a theoretical basis for the treatment of UC and further drug development.
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